In this proposal, we propose to demonstrate the feasibility of a novel ultrasound-induced thermal strain imaging (US-TSI) as clinically useful tool for quantitative assessment of fat in liver, which is critically important with growing prevalence f nonalcoholic fatty liver disease (NAFLD). NAFLD is the most common form of chronic liver disease in both children and adults and has become a serious public health problem, affecting up to 30% in the United States population. NAFLD was thought to be a benign condition but is now increasingly recognized as a major cause of liver-related morbidity and mortality, progressing to cirrhosis, liver failure, and hepatocellular carcinoma. Steatosis, the accumulation of fat-containing vacuoles within hepatocytes, is a key histological feature of fatty liver disease A simple steatosis can be reversed with proper treatments if found at early stage, however moderate to severe steatosis are at greater risk of developing chronic liver complications. A cost-effective, noninvasive imaging modality, which allows detection and quantification of fat in the liver with high sensitivity and specificity, will therefore provide accurate diagnosis at early stage and evaluation of the treatments of NAFLD longitudinally. Current diagnosis methods for NAFLD are invasive, expensive, ionizing, or less sensitive. A needle biopsy is invasive and poorly suited as a diagnostic test in such a prevalent condition because of its expense and risks of complications, especially for children. Ultrasound (US) B-scan, the most common noninvasive diagnostic imaging in current clinics, does not provide quantitative information of the degree of lipid accumulation, and is not sensitive enough to detect early steatosis. Both CT and MR scanning are more sensitive techniques for quantification of steatosis. However, they are ionizing or expensive, not suitable for children. US-TSI can noninvasively identify lipid contents in tissue. We have previously developed US-TSI using US for both imaging and heating (<3oC) for lipid detection in atherosclerotic plaques. In this application, we propose to evaluate the sensitivity and specificity of US-TSI for fat quantification in liver. The long term goal of this research program is to develop a novel noninvasive clinical imaging modality for diagnosis and treatment evaluation of fatty liver diseases. The objective within the scope of the proposed study is to develop and evaluate US-TSI as noninvasive imaging tool to assess liver fat in rodents. The evaluation will be performed systematically by computer simulation, experiments using tissue mimicking phantoms and excised liver, and in vivo mouse models. If successful, this project can be translated relatively easily into the human subject study using a commercial ultrasound scanner combined with a safe US heating source, which is the long-term goal of this research program. US-TSI will bring a highly influential impact on NAFLD, allowing an accurate disease staging, which will lead to improved treatment outcomes, preventing it from the progression to chronic liver complications. This will also lessens the medical expenses of the extended tests like MR or CT, which are not anyway suitable for children.